Genetic and clinical aspects of Zellweger spectrum patients with PEX1 mutations
Genetic and clinical aspects of Zellweger spectrum patients with PEX1 mutations
复制标题
具有 PEX1 突变的 Zellweger 谱系患者的遗传和临床方面
作者：
H. Rosewich;A. Ohlenbusch;J. Gärtner
目的：对一系列Zellweger谱患者进行PEX1基因分析，PEX1基因是导致过氧化物酶体生物发生障碍(PBD)的最常见原因。方法：采用不同的方法进行突变检测，包括SSCP分析作为一种基于基因组或cDNA的筛查技术，然后对异常电泳型的PCR片段进行直接测序。结果：33例患者纳入研究。两个常见的突变，c.2528G→A，G843D和c.2098_2098insT，I700YfsX42，占全部异常等位基因的80%以上，强调了它们的诊断相关性。大多数PEX1突变分布在两个AAA盒上，具有两个功能蛋白结构域，即D1和D2，以及高度保守的Walker基序。CG1中Zellweger谱的表型严重程度取决于突变对PEX1蛋白Peroxin 1的影响。PEX1突变可分为两种类型-表型相关性：I类突变导致残留的PEX1蛋白水平和功能，以及较温和的表型；II类突变几乎使PEX1蛋白水平和功能消失，导致严重表型。I类和II类突变的复合杂合子患者具有中间表型。结论：临床和生化诊断的分子确认将有助于预测单个PBD患者的临床病程。
Objective: To analyse the PEX1 gene, the most common cause for peroxisome biogenesis disorders (PBD), in a consecutive series of patients with Zellweger spectrum. Methods: Mutations were detected by different methods including SSCP analyses as a screening technique on the basis of genomic or cDNA, followed by direct sequencing of PCR fragments with an abnormal electrophoresis pattern. Results: 33 patients were studied. Two common mutations, c.2528G→A, G843D and c.2098_2098insT, I700YfsX42, accounted for over 80% of all abnormal PEX1 alleles, emphasising their diagnostic relevance. Most PEX1 mutations were distributed over the two AAA cassettes with the two functional protein domains, D1 and D2, and the highly conserved Walker motifs. Phenotypic severity of Zellweger spectrum in CG1 depended on the effect of the mutation on the PEX1 protein, peroxin 1. PEX1 mutations could be divided into two classes of genotype–phenotype correlation: class I mutations led to residual PEX1 protein levels and function and a milder phenotype; class II mutations almost abolished PEX1 protein levels and function, resulting in a severe phenotype. Compound heterozygote patients for a class I and class II mutation had an intermediate phenotype. Conclusions: Molecular confirmation of the clinical and biochemical diagnosis will allow the prediction of the clinical course of disease in individual PBD cases.
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影响因子：
3.8
作者：
Hiebler S;Masuda T;Hacia JG;Moser AB;Faust PL;Liu A;Chowdhury N;Huang N;Lauer A;Bennett J;Watkins PA;Zack DJ;Braverman NE;Raymond GV;Steinberg SJ
通讯作者：
Steinberg SJ
影响因子：
9.8
作者：
D. Warren;J. Morrell;H. Moser;D. Valle;Stephen J. Gould
通讯作者：
D. Warren;J. Morrell;H. Moser;D. Valle;Stephen J. Gould
DOI：
10.1073/pnas.95.15.8630
发表时间：
1998-07-21
影响因子：
11.1
作者：
Geisbrecht, BV;Collins, CS;Gould, SJ
通讯作者：
Gould, SJ
影响因子：
4.4
作者：
SHEFFIELD, VC;BECK, JS;STONE, EM
通讯作者：
STONE, EM
影响因子：
3.8
作者：
Steinberg, S;Chen, L;Braverman, N
通讯作者：
Braverman, N